The Jackson Laboratory (JAX) Center for Precision Genetics (JCPG) will develop and disseminate new, precise animal models of incurable and genetically complex human diseases. The JCPG will leverage JAX's long-established expertise in mammalian genetics and disease modeling as well as the human clinical samples, data and collaborations fostered by The Jackson Laboratory for Genomic Medicine (JAX-GM), its newly established clinical genomics institute. The JCPG's international, multi-disciplinary team-including geneticists and genetics technology experts, molecular and computational biologists, clinical experts in specific disease areas and world leaders in the development of precision animal models of disease-will possess the collective ability to foresee disease modeling needs as they emerge and will serve investigators in a variety of disease areas on a regional, national and international basis. Initially six projects will address intractable or incurable diseases linkd by genetic complexity, molecular genetic data and/or humanization that represent diverse stages of preclinical development. The JCPG will: Aim 1) Align investigator-initiated disease model research projects with institution-wide support to create efficient and goal-oriented preclinical pipelines; Aim 2) Use heuristic program development in the pilot center research projects and cores to position JAX to be a fully functional center in five years, while nevertheles achieving tangible outcomes during the pilot period; Aim 3) Embrace both realistic, cutting-edge technological platforms and ambitious high-risk, high-reward platforms as required to get the job done, i.e., advance paths to therapies for heretofore incurable diseases; and Aim 4) Through JAX's many inter-institutional collaborations, identify and engage key clinical, foundation and corporate partners, who share our vision both for specific disease objectives, to help us navigate larger center goals. Ultimately, the JCPG will generate new disease modeling processes and pipelines, data resources, research results and models that will be swiftly shared through JAX's proven dissemination pipelines to accelerate translation to medical benefit.